1. Field of the Invention
The invention relates to natriuretic peptides A(atrial), B(brain), and type C; and a novel natiuretic peptide receptor B (NPRB) having binding affinity for these peptides. The invention further relates to the synthesis and use of mammalian natriuretic peptide receptor B produced by recombinant means.
2. Description of the Background Art
Cardiovascular homeostasis is controlled by several distinct but interrelated regulatory pathways that modulate blood pressure, fluid volume and electrolyte composition. One component of this control system is a atrial natriuretic peptide (ANP), a 28 amino acid endocrine hormone that is released by ventricular cardiocytes in response to elevated arterial blood pressure and increased intravascular fluid volume..sup.2
Alpha atrial natriuretic peptide (aANP) or (ANP) and brain natriuretic peptide (BNP) and type C natriuretic peptide (CNP) are homologous polypeptide hormones involved in the regulation of fluid and electrolyte homeostasis (reviewed in 1, 2, and 31). These three natriuretic peptides apparently share common receptors and stimulate the intracellular production of cGMP as a second messenger.sup.1. Molecular cloning has defined two types of natriuretic peptide receptors. A 60-70 kd ANP-C receptor (NPRC) is not coupled to cGMP production and may function in the clearance of ANP.sup.3,4. A 120-140 kd NPRA receptor is a membrane form of guanylyl cyclase (GC) in which ligand binding to the extracellular domain activates the cytoplasmic GC domain.sup.5,6. Previous biochemical evidence (reviewed in ref. 24) had not suggested the presence of natriuretic peptide receptor-GC subtypes. The identification of an additional receptor which would bind to the two natriuretic peptide ligands, would indicate a hitherto unappreciated complexity to this system. If such a subtype existed, it would then be possible to determine the role of each of the possible receptor-GC/ligand combinations in cardiovascular regulation. Knowledge of the DNA encoding an additional ANP receptor would allow the recombinant production of novel receptor protein and could be used in diagnostic hybridization procedures for the detection of novel mammalian receptor encoding genes. The novel receptor could be used to detect additional unique natriuretic peptides or other ligands which bind.
It is an object of the present invention to provide in commercially useful quantities, novel mammalian NPRB from a therapeutically acceptable source, most preferably human NPRB. It is an additional object to prepare amino acid sequence and other variants of mammalian NPRB. Yet another object is to produce a DNA sequence encoding mammalian NPRB which will hybridize with naturally occurring DNA sequences encoding a mammalian NPRB. Still another object is to produce antibody specific for NPRB.
These and other objects of the invention will be apparent from the specification as a whole.